B-1 B cells as a source of polyreactive IgE antibodies, in allergic individuals

过敏性疾病是由称为B细胞的细胞产生的抗体分子的作用引起的。在过去的15年中，已经认识到存在至少两种B细胞亚群，称为B-1和B-2细胞。B-1细胞及其抗体产物具有许多不寻常的特征，它们与某些疾病过程有关。我们最近完成的研究强烈提示B-1 B细胞可能在某些过敏性疾病中起重要作用。我们希望比较根据过敏性疾病和年龄定义的患者组，以了解B-1 B细胞活性是否与特定的过敏性疾病相关。我们假设过敏性皮肤病患者的过敏诱导B-1细胞数量增加。这些患者将与那些对吸入性过敏原过敏的患者和其他食物过敏的患者进行比较。研究将在成人组和儿童组中进行，因为已知B-1 B细胞数量随年龄而变化。由于我们对过敏性疾病背景下B细胞功能调节的大多数理解来自于对常规B-2细胞进行的研究，我们也希望重新考虑B细胞调节的各个方面。我们特别感兴趣的是B-1 B细胞的“转换”调节，当它们从产生“非过敏”类型的抗体（IgM抗体）转变为促过敏的IgE抗体时。我们希望确定过敏个体的B-1 B细胞在被称为细胞因子的调节分子的影响下是否特别容易受到这种转换的影响。我们预计B-1 B细胞将与一些（尽管不是所有）过敏性疾病相关，并且这些细胞将成为治疗的新靶点。这样的发现将是最重要的。新疗法的开发将需要更好地了解这些细胞的调节，这将是该项目的另一个重要成果。

Allergic disease results from the actions of antibody molecules that are produced by cells called B cells. Over the last fifteen years, it has been realised that there are at least two B cell subsets, called B-1 and B-2 cells. The B-1 cells and their antibody products have many unusual features, and they have been implicated in some disease processes. We have recently completed studies that strongly suggest that B-1 B cells may play an important role in some allergic disease. We wish to compare groups of patients defined according to their allergic conditions and age, to see whether B-1 B cell activity is associated with particular allergic diseases. We hypothesise that patients with allergic skin conditions have raised numbers of allergy-inducing B-1 cells. Such patients will be compared with those with allergies to inhalent allergens and others with food allergies. Studies will be performed in adult groups as well as in children, for B-1 B cell numbers are known to vary with age. As most of our understanding of the regulation of B cell function, in the context of allergic disease, has arisen from studies conducted with conventional B-2 cells, we also wish to reconsider aspects of B cell regulation. We are specifically interested in the regulation of the 'switching' of B-1 B cells, when they change from the production of antibodies of a 'non-allergic' type (IgM antibodies) to allergy-promoting IgE antibodies. We wish to determine whether the B-1 B cells of allergic individuals are particularly susceptible to such switching, when under the influence of regulatory molecules called cytokines. We expect that B-1 B cells will be associated with some, though not all allergic conditions, and that these cells will emerge as a new target for therapies. Such a finding would be most important. The development of new therapies will require a better understanding of the regulation of these cells, and this will be another important outcome of this project.